天津医药 ›› 2021, Vol. 49 ›› Issue (2): 141-146.doi: 10.11958/20202104

• 实验研究 • 上一篇    下一篇

雷公藤红素通过抑制颗粒细胞炎症因子基因表达改善肥胖小鼠生育能力的研究 #br#

宋东红,马利方,于洋   

  1. 北京大学第三医院妇产科生殖医学中心(邮编100191
  • 收稿日期:2020-07-22 修回日期:2020-10-30 出版日期:2021-02-15 发布日期:2021-02-02
  • 通讯作者: 马利方 E-mail:21511633@qq.com
  • 基金资助:
    内质网应激介导UPR信号通路对多囊卵巢综合征女性颗粒细 胞凋亡的调控作用及机制研究;OCT1表达异常导致细胞凋亡介导PCOS女性颗粒细胞生理功能紊乱的机制 研究;Sirt4调控多囊卵巢综合征女性颗粒细胞线粒体功能的作用 机制研究

Study on the fertility improvement of obese mice by inhibiting granulosa cell inflammation using celastrol #br#

SONG Dong-hong, MA Li-fang, YU Yang #br#   

  • Received:2020-07-22 Revised:2020-10-30 Published:2021-02-15 Online:2021-02-02
  • Contact: Li-Fang Ma E-mail:21511633@qq.com

摘要: 目的 探讨雷公藤红素能否通过改善肥胖小鼠颗粒细胞的炎症因子基因表达,提高胚胎发育潜能,进而提
高肥胖小鼠生育能力。
方法通过高脂饮食建立肥胖小鼠模型,采用实时荧光定量PCRqPCR)法检测颗粒细胞炎症
因子基因、凋亡基因及激素合成相关基因表达水平,交配实验检测其生育能力,并与正常饮食组小鼠比较。对高脂饮
食小鼠喂食雷公藤红素,收集小鼠卵母细胞及颗粒细胞,采用
qPCR法检测颗粒细胞相关基因的表达水平;采用单精子
胞浆内注射方法观察卵母细胞受精率;进行胚胎移植,检测出生率等指标,并与高脂饮食组及正常饮食组小鼠相比较。
结果与正常饮食组小鼠相比,高脂饮食组小鼠体质量显著增加,颗粒细胞炎症因子基因IL-1βIL-6和凋亡基因Bax
Bak1FaddTraf2Casp8Casp9 mRNA表达水平显著升高,激素合成基因Cyp11a1Cyp19a1 mRNA表达显著降低(P
0.01),卵裂率、囊胚率及出生率显著降低(P0.01)。与高脂饮食组小鼠相比,雷公藤红素组小鼠颗粒细胞炎症因子基
因、细胞凋亡基因和激素合成基因表达显著改善(
P0.01),与正常饮食组小鼠相比差异无统计学意义。雷公藤红素组
小鼠排卵数、卵裂率、囊胚率及出生率均显著高于高脂饮食组小鼠(
P0.05)。 结论雷公藤红素可以通过降低颗粒细
胞炎症因子基因表达水平,缓解颗粒细胞过度凋亡,恢复颗粒细胞激素分泌功能,进而提高肥胖小鼠的生育能力。

关键词: 雷公藤属, 粒层细胞, 炎症, 基因, 生育力, 小鼠, 肥胖, 激素合成, 雷公藤红素

Abstract: ObjectiveTo explore the effects of celastrol on increasing embryonic development potential and fertility in
obese mice by improving the inflammatory state of granulosa cells. MethodsThe obese mouse model was established by
high-fat diet. qPCR method was used to detect the levels of inflammatory genes, apoptosis genes and hormone synthesis
genes in granulosa cells. The fertility was detected by mating experiment, and the improvement results were shown in the
comparison between the high-fat diet and the normal diet groups. Obese mice in the high-fat diet group were fed celastrol.
qPCR method was used to detect the expression of correlated genes in granulosa cells. The oocytes were fertilized by intracytoplasmic sperm injection method, and the embryonic development rate was calculated using the number of zygotes, 2-cell
embryos and blastocysts. The birth rate and other indicators were indicated by embryo transfer methods.
ResultsCompared
with normal diet mice, the inflammatory genes
Il-1β, Il-6 and apoptosis genes Bax, Bak1, Fadd, Traf2, Casp8 and Casp9
mRNA were significantly increased in granulosa cells in addition to the increased body weight, whereas hormone synthesis
genes
Cyp11a1 and Cyp19a1 expression were significantly decreased in high-fat diet mice (P0.01). The embryonic
developmental rate, pregnancy rate and birth rate of obese mice also decreased significantly (
P0.01). Compared with mice
in the high-fat diet group, the expressions of inflammation genes, apoptosis genes and hormone synthesis genes were
significantly improved in granulosa cells of celastrol group (
P0.01), and there were no significant differences when
compared with the mice in the normal diet group (
P0.01). The ovulation rate, embryonic development rate and birth rate
were significantly better in celastrol group than those in high-fat diet group (
P0.01). Conclusion Celastrol can reduce
inflammatory gene expression in granulosa cells, relieve granulosa cell excessive apoptosis, restore granulosa cell hormone
secretion function, and therefore improve the fertility of obese mice.

Key words: tripterygium, granulosa cells, inflammation, genes, fertility, mice, obese, hormone synthesis, celastrol

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